F ailure of the pancreas to secrete sufficient insulin results in type 2 diabetes, but the pathogenesis of pancreatic β cell dysfunction is still poorly understood. New insights into β cell failure come from defining the genes involved in rare genetic subtypes of diabetes and creating appropriate animal models. A new mouse model of transient neonatal diabetes mellitus emphasizes that both the number of β cells and their function are critical for insulin secretion and may be regulated by imprinted genes.